Predictors of Outcomes After Coronary Artery Bypass Grafting: The Effect of Concomitant Mitral Repair

Background Ischemic mitral regurgitation (IMR) or functional MR intensity with or without repair increases the risk of coronary artery bypass grafting (CABG), and if the contaminant is undertaken, it doubles the risk of the surgery. This study aimed to characterize patients with concomitant CABG and mitral valve repair (MVR) and assess the surgical and long-term outcomes. Methods We conducted a cohort study from 2014 to 2020 on 364 patients who underwent CABG. A total of 364 patients were enrolled and divided into two groups. Group I (n= 349) included patients with isolated CABG, and Group II included patients who underwent CABG with concomitant mitral valve repair (MVR) (n= 15). Results Regarding preoperative presentation, most patients were male: 289 (79.40%), hypertensive 306 (84.07%), diabetic 281 (77.20%), dyslipidemic 246 (67.58%), presenting with NYHA classes III-IV: 200 (54.95%), and upon angiography, found to have the three-vessel disease: 265 (73%). Regarding their age mean± SD and Log EuroSCORE median (Q1-Q3), they had a mean age of 60.94± 10.60 years and a median score of 1.87 (1.13-3.19). The most prevalent postoperative complications were low cardiac output 75 (20.66%), acute kidney injury (AKI) 63 (17.45%), respiratory complications 55 (15.32%), and atrial fibrillation (AF) 55 (15.15%). Regarding long-term outcomes, most patients reported class I NYHA 271 (83.13%) and an echocardiographic decrease in MR severity. Patients with a CABG + MVR were significantly younger (53.93± 15.02 vs. 61.24± 10.29 years; P= 0.009), had a lower ejection fraction (33.6 [25-50] vs. 50 [43-55] %; p= 0.032), and had a higher prevalence of LV dilation (32 [9.17%]). EuroSCORE was significantly higher in patients with mitral repair (3.59 [1.54-8.63] vs. 1.78 (1.13-3.11); P= 0.022). The mortality percentage was higher with MVR but did not attain statistical significance. Intraoperative CPB and ischemic durations were longer in the CABG + MVR group. Furthermore, neurological complications were higher in patients with mitral repair (4 (28.57%) vs. 30 (8.65%), P= 0.012). The study’s follow-up duration median was 24 (9-36) months. The composite endpoint occurred more frequently in older patients (HR: 1.05 [95% CI: 1.02-1.09]; 0.001), patients with low ejection fraction (HR: 0.96 [95% CI: 0.93-0.99]; P= 0.006) and in patients with preoperative myocardial infarction (MI) (HR: 2.3 [95%: 1.14- 4.68]; P= 0.021). Conclusion Most IMR patients benefited from CABG and CABG + MVR, as evident by NYHA class and echocardiographic follow-up. CABG + MVR had a higher Log EuroSCORE risk with increased intraoperative cardiopulmonary bypass (CPB) and ischemic durations, which may have played a role in increasing the incidence of postoperative neurological complications. On follow-up, no differences were reported between the two groups. However, age, ejection fraction, and a history of preoperative MI were identified as factors affecting the composite endpoint.


Conclusion
Most IMR patients benefited from CABG and CABG + MVR, as evident by NYHA class and echocardiographic follow-up. CABG + MVR had a higher Log EuroSCORE risk with increased intraoperative cardiopulmonary bypass (CPB) and ischemic durations, which may have played a role in increasing the incidence of postoperative neurological complications. On follow-up, no differences were reported between the two groups. However, age, ejection fraction, and a history of preoperative MI were identified as factors affecting the composite endpoint.

Introduction
Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure performed worldwide [1]. Several risk factors, either patient-or procedure-related, directly impact the outcomes of CABG surgery [2]. One of the important independent risk factors for increased morbidity and mortality after CABG is ischemic mitral regurgitation (IMR) [3]. Mitral valve repair combined with CABG is the recommended treatment for severe IMR; however, the management of moderate IMR is still controversial [4]. Surgical or transcatheter treatment of IMR improves survival compared to optimized medical therapy [5]. Combined CABG and mitral valve repair in treating severe IMR improves the severity of MR as compared to CABG alone [6].
There is a debate about whether to perform CABG alone or CABG combined with mitral valve repair surgery (MVR) for managing IMR; however, the most recent ESC/EACTS guidelines recommend that surgery is more likely to be considered if myocardial viability is present, mic and dilated left ventricle (LV) in the presence of normal valve leaflets, CABG alone will reverse the IMR through improved regional wall motion abnormalities, papillary muscle function, and stimulation of reverse LV remodeling without exposing the patient to increased operative risk by an additional surgical procedure [9]. Not all approaches fit all patients, and IMR is not the sole factor affecting outcomes after CABG. Thus, this study aims to assess the preoperative characteristics, intraoperative variables, postoperative events, and long-term outcomes of IMR patients undergoing either isolated CABG or CABG with MVR.

Data and outcomes
We described the preoperative demographics (age, gender, and body mass index) and comorbidities [diabetes mellitus, hypertension, dyslipidemia, previous cerebrovascular accident (CVA), chronic kidney disease (CKD), history of previous myocardial infarction (MI), and previous percutaneous coronary intervention (PCI)] in all patients and compared them between the study groups. Data on left ventricular ejection fraction (EF), left ventricular dilatation, and dyskinesia was retrieved from the latest preoperative echocardiography. Angiographic data included the associated left-main coronary artery disease, three-vessel disease, or two-vessel disease. Risk stratification was performed using the log EuroSCORE [10].
Intraoperative data included cardiopulmonary bypass (CPB) and ischemic times, left internal mammary artery (LIMA) use, and the number of grafts. Postoperative outcomes were compared between both groups. Hospital outcomes were postoperative drainage in the first 24 hours after placement, low cardiac output (LCO), re-exploration for bleeding, perioperative MI (PMI), acute kidney injury (AKI), hemodialysis, neurological complications, atrial fibrillation, prolonged ventilation, the duration of hospital stay, and mortality.
Patients' follow-ups were retrieved from the medical records. The follow-up outcomes that reflected a relatively poorer response to treatment, such as mortality, recurrence, or persistence of moderate to severe mitral regurgitation, the need for another mitral valve intervention, or repeat coronary revascularization, were grouped as the composite endpoint.

Definitions
Postoperative acute kidney injury (AKI) was defined as an increase in serum creatinine 1.5 times more than the preoperative value or the initiation of postoperative hemodialysis [11]. Neurological complications included stroke and transient ischemic attacks. Stroke was defined as the persistence of neurological impairment for more than 24 hours with radiological evidence of an ischemic or hemorrhagic insult [12]. The recent universal definition of MI is based on a rise and/or fall of cardiac biomarkers (preferably troponin) in the setting of myocardial ischemia: cardiac symptoms, ECG changes, or imaging findings. Studies using serial troponin measurements demonstrate that most PMIs start within 24 to 48 hours of surgery during the greatest postoperative stress or new regional wall motion abnormalities diagnosed with echocardiography [13]. Low cardiac output was diagnosed in the patients who required maximum inotropic support or mechanical circulatory support [14]. Prolonged ventilation was defined as postoperative mechanical ventilation lasting >24 hours.

Techniques
The surgical procedures were all performed through a midline sternotomy using standard cardiopulmonary bypass with intermittent antegrade cardioplegia. Mitral valves were inspected to confirm the preoperative echocardiographic absence of structural pathologies. In patients undergoing MVR, bicaval cannulation was used, and mitral repair was performed after the distal anastomosis. Ring annuloplasty was the procedure of choice in all patients for MVR, and it was used according to the anterior leaflet length and intercommissural distance. The goal of repair was to achieve a coaptation depth of 8 mm and no more than mild residual MR. The left internal mammary artery was the conduit of choice in most patients except in those undergoing emergency CABG.

Statistical analysis
Data were presented as mean and standard deviation or median and interquartile range for quantitative data types and numbers (%) for qualitative data types.

Preoperative and operative characteristics
The study included 364 patients who underwent CABG. Regarding the angiographic findings of the patients preoperatively, the majority presented with three-vessel disease 265 (73%), while 71 (19.56%) had the two-vessel disease. Moreover, the left-main disease was present in 104 (28.57%) patients.

FIGURE 1: The relationship between EuroScore and mitral regurgitation grade (MR)
The
There were no differences in drainage, re-exploration for bleeding, perioperative MI, acute kidney injury (AKI), new-onset dialysis, postoperative atrial fibrillation (AF), or the length of hospital stay between the groups.
The mortality rate was higher in mitral valve patients but was not statistically significant, whereas CABG + MVR was associated with significantly higher neurological complications ( Table 2).

Follow-up
Upon follow-up, the median duration of follow-up was 24 (9-36) months, and 342 patients were available for follow-up. As shown in Table 3, by echocardiographic evaluation, 288 (92.6%) had no increase or persistence of MR severity, but the recurrence or persistence of moderate or severe MR, defined as the recurrence, refers to the worsening or returning of the mitral regurgitation abnormality after a successful CABG or repair, was found in 23 (7.4%) patients who had evidence of MR preoperatively. These 23 patients are from the group who underwent isolated CABG. Moreover, 314 (96.32%) reported NYHA classes I-II; however, there was no statistically significant difference in NYHA classes III and IV at the last follow-up between groups 11 (3.51%) vs. 1 (7.69%), P= 0.392. Furthermore, 17 (4.96%) were reported as deceased; however, no statistically significant difference was present between both groups. In addition, three (0.89%) required an additional mitral procedure, and 25 (7.4%) required revascularization.

Factors affecting the composite endpoint
As shown in Table 4 [16,17]. This study aimed to assess the preoperative characteristics, intraoperative variables, operative events, and long-term outcomes of IMR patients undergoing either isolated CABG or CABG with MVR. Moreover, we evaluated factors affecting the outcomes after CABG.
Regarding the baseline characteristics of the patients enrolled in this study, the majority of our patients were males, with no difference in gender distribution between CABG alone and CABG + MVR. This could be attributed to the higher prevalence of coronary artery disease in men, as concluded by Jamee et al. [18]. The most common comorbidities in our patients were hypertension, followed by diabetes mellitus, which is consistent with a nationally based study by Murray et al. about risk factors for coronary artery disease [19]. Patients with mitral valve repair were significantly younger and had a lower prevalence of hypertension and diabetes. This may be explained by the fact that patients who are considered better candidates are elected for combined CABG and MVR surgery. EF was significantly lower in CABG with MVR patients; moreover, these patients had a higher prevalence of LV dilatation. Kim and associates [20] reported comparable characteristics between patients with CABG alone versus CABG and mitral repair. However, patients with mitral repair had a significantly lower EF. The variations in preoperative variables in our series could be attributed to several factors. Patients who had repair tended to have a higher degree of MR with LV dilatation and impaired LV function. Additionally, MVR patients had a higher EuroSCORE, and we found a proportional relationship between IMR severity and EuroSCORE.
We did not find a difference in postoperative outcomes between both groups apart from higher neurological complications in combined CABG + MVR surgery. Despite being younger and having a lower prevalence of DM, increased neurological complications could be attributed to the increased complexity of undergoing concomitant CABG with MVR with prolonged cardiopulmonary bypass and ischemic times in addition to having a higher log EuroSCORE, a higher prevalence of LV dilation, and a lower median EF. Operative mortality was not significantly higher with MVR. The length of hospital stays did not differ significantly between groups. These results partially contradict Kim and colleagues' study [20]. They reported higher neurological and cardiac complications, low cardiac output, and mortality in CABG and MVR patients.
During follow-up, recurrence or residual MR was higher in the CABG-only group. The composite endpoint did not differ significantly between groups. Our results are similar to those of other series, which found no difference in long-term outcomes between CABG with and without MVR. Bouchard and associates found no difference in EF and LV dimensions after 12 months between CABG alone and CABG and MVR [21]. Fattouch et al. [22] found that concomitant MVR was associated with improved EF, LV dimensions, and symptoms, while there was no difference in short-term survival. Similarly, Chan and colleagues [23] reported improved outcomes after MVR in their randomized clinical trial comparing CABG vs. CABG and MVR. The difference in outcomes between randomized trials and retrospective studies could be attributed to the strict inclusion criteria and the exclusion of high-risk patients.
Risk factors for the composite endpoint were age, low EF, and preoperative MI. CABG is the preferred treatment in patients with low ejection fraction and has superior outcomes compared to PCI [24]. Awan and associates [25] found that low ejection fraction is an independent risk factor for mortality in patients undergoing isolated CABG. Similar to our study, Nuru and colleagues [26] found that the risk of CABG increased in older patients. These results indicate that patient-related risk factors play a significant role in determining the long-term outcomes after CABG.
Regarding the limitations of the study, most of our patients underwent revascularization with CABG only, which can skew the data toward the latter group. In addition, patients who underwent CABG + MVR were relatively fewer in number compared to the CABG group. This issue, in addition to having a single-center study, might affect the generalizability and reproducibility of the results. Moreover, due to following a convenience sampling technique, this study is vulnerable to selection bias. Several variables may confound the outcomes and were not measured in our patients. Furthermore, the low number of postoperative events may obscure the statistically significant levels.